title: A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.
abstract: OBJECTIVE
  Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.
  
  
  METHODS
  RA patients (n=212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates.
  
  
  RESULTS
  An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors.
  
  
  CONCLUSIONS
  The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Strausbauch
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Crowson
authors.forename: Terry M
authors.initials: TM
authors.lastname: Therneau
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wettstein
authors.forename: Veronique L
authors.initials: VL
authors.lastname: Roger
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
authors.forename: Sherine E
authors.initials: SE
authors.lastname: Gabriel
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology*
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines